What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

Azithromycin is the recommended first-line treatment for uncomplicated typhoid fever, with a dosage of 20 mg/kg/day for 7 days, particularly in children and pregnant women due to its safety profile. 1

First-line Treatment Options Based on Resistance Patterns

Treatment should be guided by local resistance patterns, as multidrug resistance is increasingly common:

For fully sensitive Salmonella Typhi:

• First choice: Azithromycin (20 mg/kg/day for 7 days)
• Alternatives: Fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole

For multidrug-resistant strains:

• First choice: Azithromycin or ceftriaxone
• Alternative: Cefixime

For quinolone-resistant strains:

• First choice: Azithromycin or ceftriaxone
• Alternative: Cefixime

Evidence Supporting Treatment Recommendations

• Azithromycin achieves faster fever clearance times (<4 days) and higher clinical cure rates compared to other antibiotics, with relapse rates <3% 1
• In regions with high rates of multidrug and nalidixic acid resistance, both gatifloxacin and azithromycin have shown excellent efficacy and safety profiles 2
• 96% of Salmonella Typhi isolates show resistance to nalidixic acid and 58% are multidrug-resistant, highlighting the importance of using newer antibiotics 1, 2
• Ciprofloxacin is FDA-approved for typhoid fever caused by Salmonella typhi, but resistance is common in South Asia 3, 4

Treatment Duration and Monitoring

• Standard treatment duration is 7 days for uncomplicated cases
• Consider changing antibiotic regimen if no improvement is seen within 2 days of starting treatment 1
• Monitor for clinical response, including fever clearance, which typically occurs within 3-4 days of starting appropriate therapy

Special Populations

• Children and pregnant women: Azithromycin is preferred due to its safety profile 1
• Immunocompromised patients: Consider longer duration of therapy and may require alternative treatment options such as ceftriaxone 1
• Severe or complicated typhoid: Intravenous ceftriaxone may be required initially

Emerging Resistance Patterns

• Extensively drug-resistant strains have emerged in Pakistan, resistant to ciprofloxacin and ceftriaxone 4, 5
• Treatment choice should be guided by local resistance patterns, particularly in South Asia where fluoroquinolone resistance is common 4

Prevention

• Typhoid vaccination is recommended for travelers to endemic areas 1
• Proper hand hygiene is essential to prevent transmission, especially after using the toilet and before food preparation 1

Common Pitfalls to Avoid

1. Using fluoroquinolones as first-line in South Asia without checking resistance patterns
2. Not adjusting therapy if clinical response is inadequate after 48 hours
3. Using inadequate treatment durations (less than 7 days)
4. Not considering alternative diagnoses in cases of treatment failure

The treatment landscape for typhoid fever continues to evolve with changing resistance patterns, making it essential to stay updated with local antimicrobial susceptibility data when selecting appropriate therapy.